Premature birth (PTB) is a significant public health problem. The technological advances in newborn intensive care of the past decades have increased survival of preterm infants and the awareness of the need to improve outcomes. Infection-induced PTB represents a unique environment, given that attempts to prolong pregnancy raise the risk for early onset neonatal sepsis (EONS). In such cases, there is an increased risk of poor neonatal outcomes, including intra-ventricular hemorrhage (IVH), which is a significant cause of brain injury, cerebral palsy and developmental disability. A key problem is that most hemorrhages occur in the first 24 hours and therapies aimed to prevent IVH must address the complexity of this condition. In 2001 the World Health Organization established the external Child Health Epidemiology Reference Group (CHERG) to develop epidemiological estimates for the various etiologies of death in young children.1 In 2003, building on the work of CHERG, it was established that prematurity accounts for 75% of infant mortality and 10% of the 10.6 million yearly deaths in children younger than five years.1 The latest U.S. vital statistics (2007) report a 12.7% rate of PTB.2 Compared to 1990, the percentage of infants delivered <37 completed weeks of gestation has climbed 20%, resulting in ˜550,000 premature infants born annually; 60,000 of them have a birthweight <1,500 grams. As support in the NBSCU has improved, more low- and very-low-birth weight (VLBW) infants survive. It has thus become clear that improving neonatal outcomes associated with prematurity is vital.3,4 About 5% of the nearly 55,000 preemies who survive the newborn period exhibit cerebral palsy and up to 25-50% have sensorial, cognitive and behavioral deficits which include mental retardation, visual and hearing impairments, learning and language disabilities, attention deficit-hyperactivity disorder, motor coordination defects, behavioral, emotional and social difficulties. The immediate impact of PTB for society is underscored by the rising costs of caring for premature infants which in 2005 was estimated in the US in excess of $26 billion/year. This figure does not include rehabilitation or long-term care costs.5 Even more concerning have been the recent childhood outcome results of studies aimed at preventing PTB by universally extending pregnancy. The results of ORACLE I & II clinical trials, released in 2008, show that antibiotics given to women in preterm labor and PPROM to increase the duration of gestation also increased the risk of cerebral palsy.6,7 The underlying mechanisms remain unclear, but this data highlights the need for a paradigm shift in prematurity research from the unilateral goal of extending the duration of gestation to concurrently improving neonatal outcomes. Concerned by these issues and the alarming increase in the rate of PTB, the March of Dimes Scientific Advisory Committee on Prematurity8 and the most recent report issued by the Institute of Medicine in 2008: Preterm Birth: Causes, Consequences and Prevention suggested that studies to identify biomarkers that may predict adverse outcomes for infants born preterm to allow for early intervention should become a priority.9 Clearly, additional approaches to assessing neonatal and early postnatal risk independent of gestational age (GA), and particularly approaches that can provide an early diagnosis, are needed.